The overall objective of the proposed research is to obtain information on how removal of a primary tumor or therapeutic manipulation by intratumor inoculation of non-specific stimulating agents, radiation or combination of the two prior to its removal affects host immunity and influences kinetics of metastases. Host and tumor responses observed will be correlated with the fate of the metastases, (growth, inhibition or elimination), resulting from therapy. To the present we have evaluated certain host cellular and non-cellular immune responses to an untreated tumor in the absence of metastases and how removal of a tumor alters those responses. It is now meaningful to determine how those responses occurring following tumor removal are affected by the presence of varying degrees of metastases. We have developed a chemo-immunotherapeutic regimen in which the most effective control of both local and distant tumor (C3H mammary) resulted from therapeutic manipulation of a primary tumor prior to its removal. As a direct extension of these two lines of investigation, we plan to determine how prior manipulation of a tumor affects hosts responses while the tumor is present and subsequent to its removal. Because of evidence suggesting that removal of a tumor may alter growth kinetics of metastases it is appropriate to determine how therapeutic manipulation of a tumor prior to its removal affects the kinetics of metastases. Since host changes or metastatic kinetic changes occurring following removal are only apt to be meaningful if they affect the fate of metastases it is necessary that the host changes be correlated with the variable response of metastases to therapy. Finally, information will be obtained on the influence of a primary tumor on the localization of effector cells in the region of metastases - an unfulfilled aim from our original proposal. In all experiments in this proposal the term "host immunity" or "host changes" refers to a battery of evaluations of cellular cytotoxicity and non-cellular responses. Both microcytotoxicity and colony inhibition by regional lymph node cells, cultured macrophages, spleen cells, bone marrow cells and blood granulocytes and lymphocytes will be determined. The non-cellular responses serum inhibition and serum cytotoxicity will be assayed.